Background: Alpha-Lipoic acid (ALA), is an antioxidant endogenous substance. It is available in small amounts in food. Mesenchymal stem cells (MSCs) derived microvesicles (MSC-MVs) have numerous paracrine protective effects against tissue injury that are mediated by inflammatory, apoptotic and oxidative stress.  Aim of the Work: Our study was done to assess the protective effects of Alpha Lipoic Acid versus MSC-MVs on indomethacin-induced gastric ulcer in rats.  Material and Methods: Forty adult male rats were divided into: Group I (10 rats) represented control animals, and Group II (30 rats) involved ulcerated rats. The ulcerated group received a single gavage of indomethacin (30mg/kg B.Wt.) and was equally subdivided into: Subgroup ΙΙ-a (ulcerated subgroup), subgroup ΙΙ-b ulcerated rats that received a single intravenous dose of MSCs-MVs (0.5 mg/mL) and subgroup ΙΙ-c ulcerated rats that received ALA (100 mg/kg) orally for 3 days before ulcer induction. Antioxidant enzymes and ulcer index were assessed. Gastric tissue was examined by light and transmission electron microscopes.
Results: Indomethacin caused marked damage of the gastric mucosa and ulcer index was significantly higher as compared to the control group. There was loss of the normal histological architecture and inflammatory cells infiltration. Ultrastructure sections revealed increased mucin granules in surface mucous secreting cells. Parietal cells showed dilatation of intracellular canaliculi. In ALA and in MSCs-MVs treated rat groups, there was a significant increase in antioxidant enzyme activities. The structure of the mucosa was significantly improved with a significant decrease in gastric ulcer area. Erosions, necrosis and inflammatory cell infiltration were significantly decreased. No major damage of endothelial cells was observed. The parietal cells count and the VEGF -positive cells were significantly decreased as compared with the control group.  Conclusion: MSCs-MVs have significant superior therapeutic effects on gastric mucosa against indomethacin-induced gastric ulcer than the protective effects of α-Lipoic acid (ALA).